CRISPR is definitely an awesome technology, and I'm glad that after many decades of research, we're finally getting approved treatments as a result.
That being said, I do want to clarify that this isn't a "cure" for sickle cell disease. It is not editing the gene causing sickle cell itself, but rather allowing for increasing production of HbF (fetal hemoglobin) by knocking down a suppressor. Hydroxyurea, a current standard of care option in sickle cell disease, also increases HbF production but response can be variable among patients (but when it works, absolutely improves quality of life!)
In addition, I think we always need to keep in mind potential toxicities and hopefully, we learn more about this when the publication actually comes out. It's important to note that giving this therapy requires giving high dose chemotherapy beforehand, and I'd also be interested in knowing how long this therapy actually lasts as I do expect the product may wane with time.
But still, so excited to see CRISPR technology coming to the public and the potential for this technology in many different disease states!
Would people who undergo this treatment become (more) vulnerable to malaria ? This is one potential side effect that was mentioned on a podcast about CRISPR. Something along the lines of "don't underestimate the 'potential benefits' of genetic disorders"
I honestly don’t know, but qualifying as a “cure” doesn’t require fixing the original thing that was broken.
Whether something is classified as a cure or treatment just depends on the extent and permanence of its effectiveness.
Is that not what’s happening here?
My goddaughter (and her older brother) have sickle cell. Her parents have been hoping and praying for some development in this field for years now. It’ll still be a while before they can obtain this treatment in Canada, but suffice it to say, it’s likely to be cured in their lifetime.
It is debilitating and affects a lot of their everyday life. I’m really happy this is progressing.
For what it’s worth my grandfather researched sickle cell and found that l-citrulline supplementation greatly improves quality of life for people with sickle cell. Unfortunately sports supplementation and erectile dysfunction treatment was the more lucrative of his patents and he died before he could finish FDA approval work for treatment of sickle cell anemia (not a cure). As citrulline isn’t expensive no one was willing to pick up his research. He provided citrulline to his patients throughout his life as their quality of life improved dramatically as to be entirely normal. I don’t know that anyone kept track of them after his death, but his research into citrulline for other purposes such as erectile and exercise performance ensured that it’s widely available now.
You can purchase it from many places but this manufacturer has a good reputation:
BULKSUPPLEMENTS.COM L-Citrulline Malate 2:1 Powder - L Citrulline Malate Supplement, Citrulline Malate Powder - Unflavored & Gluten Free - 3g per Servings, 333 Servings, 1kg (2.2 lbs) https://a.co/d/fzNovRX
Citrulline is extremely safe in any quantity. Any excess is urinated out.
I know this will sounds like a random interneter virtue signaling or karma whoring...but I'm pulling for them buddy, truly!
Similar treatment already approved by the UK 
It's fairly expensive: "estimates suggest that it could cost roughly US$2 million per patient, in line with the pricing of other gene therapies."
I assume it's a long and labour-intensive process?
Small correction: this is the same drug as the one already approved by the UK.
This is absolutely awesome. I look forward to finding out if this has an effect on the germ line as well. Imagine, ending genetic illnesses like these for the rest of human history. I look forward to forgetting these diseases even exist, except in the archives of medical history.
We could eliminate heart disease, which is still the number 1 killer of men, women, in the US, and globally.
I watched a special on this and all interviewed scientists were drastically against any germ line edits (as in something that would then be passed to offspring) as we simply don't understand things well enough yet. Some groups will eventually do this in a less regulated nation, but for now we have to be very careful.
No, this treatment would not - it does not act by "fixing" hemoglobin S (which causes sickle cell disease), but rather increasing production of hemoglobin F (fetal hemoglobin).
This particular treatment can't. They perform the gene editing on cells outside of the body before transplanting them back into the patient.
Editing the germline is a terrible idea. Governments should instead fund IVF with genome sequencing of the embryos so that you can pick an embryo that doesn't have the disease. Of course only for people with genetic diseases.
I read of a guy using a virus to deliver the DNA to his gut to fix his lactose intolerance. That was the first thing I read that made me feel more comfortable with the idea of gene therapy.
I'm not readily finding an explanation for how CRISPR works that makes sense to me and the current top comment* indicates this isn't actually a cure. I was hoping to get some idea of how CRISPR and a virus delivery mechanism compare.
What do you think about mandatory DNA screening? I.e. analyse DNA of everyone who wants to have children and do not allow it if there are defective genes? This way we could save a lot on research and treating currently incurable diseases (there would be no children with such diseases and no need for treating them).
Sounds like a great idea, we could even have people who aren't allowed to breed wear a nice yellow star on their chests so everyone knows.
I wonder why no one ever thought to implement such a thing?
I would rethink that if I were you.
How is it enforced, and how do we decide which diseases trigger this?
Between this and mRNA vaccine technology the future of medicine is looking bright
And AlphaFold! Which is a game changer for drug development.
And Brain-Computer Interfaces.
And expensive...and out of reach of most of the people who need it.
Obligatory reminder of the "fun" fact that sickle cell disease leads to a sort of partial malaria resistance, which explains its perseverance in the human gene pool.
That's "sickle cell trait" which is when you are only carrier but do not have the disease. With the disease, malaria is even more deadly.
Type O blood can also protect against severe malaria where the uninfected blood cells stick around one that is infected.
They are trialing a malaria vaccine now too. What if at birth we all got that malaria vaccine and a crispr that made everyone a carrier of sickle cell, but not germ line. That seems like we could wipe out both sickle cell and malaria.
If it benefits or isn’t detrimental to shareholders..
Given that Sickle Cell Disease only affects ~20 million people in the entire world , and beta-thalassemia affects even fewer (maybe ~200,000 people) , and that this treatment currently costs millions of dollars per person, I think shareholders will be just fine.
Realistically, this treatment is not going to be available in places with a high prevalence of malaria for a long time, so I don't think this is too much of a concern.
Wouldn’t they just become equal likelihood of getting it compared with people without sickle cell?
This means most people on the planet I think. You could just take a malaria pill.
Technically no it doesn't. I had thought that curing did mean fixing the problem, but I just googled and it does indeed also mean relieving of the symptoms.
But I think in this case they're right to clarify. I think the low level of common knowledge around gene editing could lead people to believe that this is mutating the sickle cells into healthy cells, which it isn't doing
> I had thought that curing did mean fixing the problem, but I just googled and it does indeed also mean relieving of the symptoms.
Usually curing would mean fixing the problem, or more specifically it would mean permanently eliminating the symptoms. This contrasts with "treatment" temporarily relieving the symptoms.
> Being cured of a disease means it’s completely gone and isn’t coming back. For many people, cures represent the ultimate treatment goal. Most diseases and conditions aren’t curable.
(This link disagrees with my use of "treatment", saying that "treatment" is any procedure, and "cure" is one of many possible outcomes of a treatment, with temporary relief being another possible outcome. But the point stands that curing definitely does mean fixing the problem.)
Glasses do not cure myopia, but they are so effective at relieving the symptoms, in an inexpensive and noninvasive way, that there is no real need for a cure.
> but I just googled and it does indeed also mean relieving of the symptoms.
In that sense AIDS is also cured, but in my book it's not, because people with it have to take pills for the rest of their lives and those pills do have serious side effects.
It might clarify how it actually works, but he’s saying it’s not a cure, and if that’s not factually correct that’s not a good thing.
That's fair, this definitely may be a functional cure for many people and that's absolutely something to be celebrated.
The language around "cure" is complicated in general. We often use it in diseases like cancer but with modern therapies, we do have some patients on long-term therapy making their cancer more of a chronic one - are they cured? On the other hand, we rarely use the word cure with diseases like hypertension or diabetes which can devastating diseases in their own right but can be controlled effectively with medication.
So yes, what should really matter is the actual outcomes - are people living longer? Is their quality of life better? And, with exa-cel/Casgevy, the latter is absolutely true (and the first will be known after time).
Actually, you’re flat out wrong. I have an incurable genetic condition. Unless it is BANG AFTER THIS NO MORE SYMPTOMS then no, it’s just another treatment.
Cure means gone. That’s why Cancer people talk about remission. I’m old enough to remember the talk around curing cancer and then it came back and killed people the medical community walked it back.
I think people are downvoting your answer incorrectly.
Best I can tell that’s because you used the word SUPPLEMENTS in all caps which is reminiscent of spam email.
However, while I can’t validate anything about your grandfather what you’re saying seems plausible and some papers have talked about it.
Perhaps! That’s just the auto formatted text from an Amazon share link on iOS - no referral code in the link!
His patents were exhaustively written and documented in medical textbook style (rather than legal robot style) further detailing the variety of uses of citrulline:
The essence is arginine is crucial in the production of NO, which serves many functions of the body but it’s also a powerful vasoprotector. Sickle cell is popularly thought to cause anemia due to the cell shape not carrying enough oxygen, but in fact it’s due to the shape irritating the epithelial cells lining blood vessels, particularly small vessels and capillaries. This redirects the use of arginine in the body to repairing and protecting the blood vessels in the body.
Citrulline is an intermediate non essential amino acid found in high concentration in watermelon seeds (hence the name). It survives the gut, unlike direct arginine ingestion, and converts readily to arginine in the kidneys (my grandfather was an expert in kidney function and pioneered kidney transplants in the 1950’s and 1969’s, his interest in sickle came late in his career in the 1990’s).
He was also an expert in heart disease, and as a young man was a tenured professor of medicine at University of Kentucky, chair of cardiovascular research, and an endowed member of the Kentucky Heart Association. He left Kentucky to found the first regional hospital and medical school in eastern North Carolina, ECU, where he was the director for many years. He was a terror of grad students, never accepted outside grant money for any of his research, never worked with drug companies, and led the bioethical research boards at his medical school for most of his career. He earned the nickname Dr House for his remarkable ability to diagnose obscure diseases and conditions along with novel treatments using his encyclopedic knowledge of biochemistry and disease, as well as his often obnoxious personality. The university forced him to retire because he brought no funding and had an entire floor for his lab when he was in his late 70’s, so he tore out his garage and built a laboratory in its place where he spent the rest of his years self publishing new research.
I think their concern is whether the public healthcare system will actually cover the cost. I think they should and will. Certainly cheaper than all the other treatments over the course of their lifetime.
I think it’s possible folks may protest against it for cost reasons but also for the eugenics-slippery-slope argument. I hope that doesn’t happen.
... Who hurt you?
You can say express your empathy and care without it being compromised.
"virtue signaling" is typically used as a pejorative by people who are unable to experience empathy for others, or at least others who aren't like them. They assume, by projection, that it's disingenuous.
(not a commentary on your parent comment)
Gene therapies are being priced according to the annual costs of treatments they replace, not the cost of producing the gene therapy product or the value of the cure to the patients.
For example, Hemgenix is a gene therapy for hemophilia. It is a single-dose product priced at $3.5 million . It's not CRISPR-based, so it's not an apples-to-apples comparison with the sickle-cell treatment discussed in the article. But I know from officials at the World Federation of Hemophilia that the direct costs of production and administration for Hemgenix are around $50,000. That's two orders of magnitude less than the list price.
The $3.5 million figure was likely arrived at because the existing products for hemophilia cost north of 350k annually, and Hemgenix is estimated to replace them for 8+ years.
> But I know from officials at the World Federation of Hemophilia that the direct costs of production and administration for Hemgenix are around $50,000. That's two orders of magnitude less than the list price.
That doesn't account for the R&D effort which has to be recouped during the runtime of the patent. Depending on whom you ask, that can reach into billions of dollars , and there's just about 200k people diagnosed with some form of hemophilia of which only a fraction has the funds or the insurance to obtain that kind of treatment in the first place (both the current and the new one), so these few patients have to account for the R&D cost of the medication, the R&D cost of failed candidate substances, the R&D for ongoing other medication and profits. For "orphan diseases", these economies are a serious problem.
Pharmaceutical development is incredibly expensive; to make it worse a lot of governments have cut back drastically on fundamental R&D grants for universities and so private companies with their profit interests stepped in.
Given the resources consumed by sickle cell patients, who often require multiple lengthy hospitalizations I bet it would be close to breakeven even at this price
The cynic in me says that it was probably priced to cost exactly the same as the expected lifetime expense of treating of the disease.
Would insurances cover it on the basis like that? I wonder if there is any similar medicine that is covered for a similar total treatment reason.
yes, they extract the cells from the patient, then crispr them in a lab with a complex protocol, and then inject them back into the patient.
But it's a cure, not a treatment.
Is it just the once. Or do you have to have repeated infusions?
As with everything though, prices for experimental procedures and devices are vastly higher than the asymptotic cost of production. There's nothing about a CRISPR process that cannot in principle be automated, it's just that right now it involves an army of lab techs with pipettes.
Why does it have to be so expensive? Just because they "can"?
The Human Genome Project to read a full copy of the base pair sequence in one human started out with about 3 Billion dollars in initial funding, and it took a couple of decades to get complete coverage.
However, the technology, techniques and equipment developed to automate the process have massively cut costs and increased speed over that time.
> A new speed record in DNA sequencing may soon help families more quickly find answers to difficult and life-altering questions.
In just 7 hours, 18 minutes, a team of researchers at Stanford Medicine went from collecting a blood sample to offering a disease diagnosis. This unprecedented turnaround time is the result of ultra-rapid DNA sequencing technology paired with massive cloud storage and computing.
You have to crawl before you can run.
We don't have a lot of experience with taking cells out of the human body, processing them, and then putting them back in. A significant amount of the cost, above and beyond the R&D required to develop the treatment and the cost of actually performing the cure, comes from extreme quality control measures that reduce the chances of infection and other problems. Also, you have to basically run a full, certified lab and house it with people qualified to perform the cure.
Everything about this is bespoke (each treatment is based on the individual cells of a patient) and artisanal (the process requires a highly skilled individual to complete), and run by a guild (only so many people are allowed to run gene therapy trials).
On the other hand, since this is a cure, and probably reduces long-term medical care costs, it could very well actually be "cheaper" in the long run, which incentivizes the government to treat as many people as possible.
That's a complicated topic, but the short version is cost of this treatment needs to cover the R&D costs to develop it, plus the costs for all the other failed experiments that didn't work out.
Plus gene therapy is in its infancy, so everything here is going to be novel and expensive. Novel treatments generally have a limited audience with even fewer practitioners, so you can't spread the R&D costs across many patients.
Prices will go down with time as patents expire and competitors emerge and this line of treatment (perhaps) becomes mainline, but that's on a ~20 year timeframe.
Because right now, it's a very bespoke process. Very low supply, with a lot demand.
As more people become proficient at this treatment, the cost will come down. But to truly get it down to reasonable amount will require automation, and we're a long way off from automating crispr.
It’s the price money you get for being the first to bring the cure to patients.
The research and the approval are extremely expensive and risky. Without a boatload of cash at the end of the tunnel, nobody would do it.
Patents will expire and in a generation, this will become cheap.
That trial was specifically for familial types of hypercholesterolemia, which are strongly genetic. Not clear that it would also work for run-of-the-mill high cholesterol, although it is possible.
Fair point. I subscribe to the idea that LDL causes heart disease:
> Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel https://pubmed.ncbi.nlm.nih.gov/28444290/
The trial inhibited PCSK9, and this study says "other PCSK9 mutations result in unusually low concentrations of plasma LDL cholesterol and a reduced risk of atherosclerotic disease". https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079795/ I'm optimistic about this.
"Eventually" already passsed five years ago.
I remembered that, but since it was an isolated incident chose to ignore it. I meant at some point China or some other country is going to just give a blanket approval or just not enforce any restrictions and then the game is on.
It seems like we should collectively decide on a reasonable pathway to germ line edits for single gene disorders. If we don’t and keep waiting, someone will do it somewhere. And once the taboo is broken things might get weird in a hurry of the global scientific and medical communities aren’t prepared.
> seems like we should collectively decide on a reasonable pathway to germ line edits for single gene disorders
Genuine question: why? Isn't the argument against germ-line editing one for diversity? If so, it seems fine to have some populations who ban it while others experiment with it.
I imagine this wouldn't be a huge issue with women since they don't produce eggs after birth, but men continue to produce gametes for life. Is there a way to prevent the introduction of the CRISPR edits to spermatocytes? Or do you just have to bank sperm and sterilize as a condition for the treatment?
They’re targeting specialized cells that make blood cells outside of the body. Once they’re reimplemented they don’t move around.
Speaking generally, I think you could perform something like this on sperm stem cells. Sperm turn over (the full population dies and is replaced) fairly quickly, but the stem cells last a long time.
It seems more likely they would just, uh, collect a sample of a single sperm cell and treat that, then use it with a treated egg using IVF.
These scientists could not publicly and unambiguously condone this for the fear of being singled out and picked out as "playing god" extremists.So they have to say the platitudes about "being careful" and ethical concerns.
However, when you suffer all your life from a genetic disease such as, say, the sickle cell or diabetes type 1, it is very obvious that it is any delay or hinderance in this direction that is deeply unethical, not the practice. Your germ line gets hundreds of random mutations at every conception, and your gamets get tons more mutations and errors as you age. It's not a dynasty hairloom.
So you think parents should not know and should not care whether their children will have an incurable disease?
According to Wiki: "Sickle cell disease occurs when a person inherits two abnormal copies of the β-globin gene (HBB) that makes haemoglobin, one from each parent". So basically this disease is encoded in DNA and it can be predicted whether future child will inherit it. Mandatory DNA screening could result in zero people having this disease (and other expensive to treat or incurable diseases). There will be no need to spend large money researching it, and those money can be used for more important non-genetic diseases.
Of course, religious people would be against this but we as a society should rely on science, not on blind faith.
> analyse DNA of everyone who wants to have children and do not allow it if there are defective genes?
You trust the government to decide who can and can't reproduce? You see no problem with this?
You see no room for abuse here?
There's already tests to show parents many diseases detected early on. It's just not mandatory to terminate.
So you think parents should not check whether their genes contain markers for incurable diseases? Let more sick children be born? With prices like several million dollars for the cure for this disease, majority of parents (except for rich countires) will not be able to afford treatment.
According to Wiki, "Sickle cell disease occurs when a person inherits two abnormal copies of the β-globin gene (HBB) that makes haemoglobin, one from each parent". So this is a disease caused by errors in DNA sequence and it can be predicted whether the child will have it.
There's a difference between having an ability and un-incentivized choice to do something, and being mandated to do that something.
One of those ends with millions of people in camps. I'll let you think about which one it is.
As I understand the most difficult to cure and incurable diseases are those that are encoded in DNA (DNA contains errors and invalid sequences which cause the disease). So instead of making multi-billion research and cure that costs millions of dollars, wouldn't it be easier to make everyone check their DNA and warn about presence of invalid sequences causing diseases? So that no more sick children are born and no need to buy pills for millions of dollars.
The DNA testing should be mandatory for everyone, but let parents decide for themselves if they want a child with an incurable disease. Maybe we should make them pay extra taxes if they ignore the warning.
mRNA editing is actually disturbingly cheap and easy to do (relatively speaking).
With the right preparation and equipment, it could be a highschool science class project.
mRNA isn't necessarily. The custom made cancer ones are, but that's different.
The government literally gave away mRNA vaccines.
Nonsense. India started pumping out covid mRNA drugs for dirt cheap in just a few months.
malaria is an interesting one where multiple antimalarials have been developed and then lost efficacy.
Doesn't it only affect Africans?
The trait is present in up to 3% of births in some parts of sub-Saharan Africa.
* About 1 in 13 black babies are born with sickle cell trait.
* About 1 in every 365 black babies are born with sickle cell disease.
* People who come from Hispanic, Southern European, Middle Eastern, or Asian Indian backgrounds can also have sickle cell disease.
* Of the 74 817 hospitalized for sickle cell disease (2016 to 2018), 69 889 (93.4%) were Blacks, 3603 (4.8%) were Hispanics, and 1325 (1.8%) were Whites.
>Usually curing would mean fixing the problem
No, I believe you’re thinking of “problem” in a different way.
A cure permanently relieves symptoms of a disease. The symptoms are what’s “gone and is never coming back.”
That much alone is called a “functional cure”, it’s not just a treatment.
The difference between a cure and a functional cure depends on the disease but in either case, it means it’s not coming back.
> No, I believe you’re thinking of “problem” in a different way.
> A cure permanently relieves symptoms of a disease.
This is a surreal correction for you to make after selectively quoting the first half of my sentence. Let's look at the whole thing:
>> Usually curing would mean fixing the problem, or more specifically it would mean permanently eliminating the symptoms.
Did you have something to add to that?
The definition relates to a treatment not the disease.
In your example the question would be, does antiretroviral therapy cure HIV? It does reduce the viral load but not permanently, so no, its not considered a cure.
The answer might change with the treatment. Does a stem cell bone marrow transplant eliminate HIV? Yes, permanently as far as it’s known so HIV is “cured” in this case.
That agrees with the point I was making. They are clarifying that this doesn't make the disease go away, but it sufficiently treats it to the point where it would have little to no effect.
So it's a cure for some definitions of cure, but not all
Virtue signaling is a common thing and also used as a pejorative.
What I find interesting is there is some cultural tension around how much to discourage such public displays. Donations can do good even if the gift giver is simply trying to improve their image. Ex: "Beware of practicing your piety before others in order to be seen by them; for then you have no reward from your Father in heaven. So whenever you give alms, do not sound a trumpet before you, as the hypocrites do in the synagogues and in the streets, so that they may be praised by others. Truly I tell you, they have received their reward.“ Notice how there’s zero implication that the behavior is negative and even an acknowledgment that doing so brings rewards, just the suggestion that it’s just not pious.
I think you're misunderstanding the verse you're quoting. The part you quoted basically says they already got their crappy reward and that's all they'll get. They won't be getting the good stuff. Don't be fake, do what's right even when nobody is looking.
>used [...] by people who are unable to experience empathy for others
The irony of this statement seems to be lost on you.
Noted and agreed on R&D costs (especially failed candidates).
> there's just about 200k people diagnosed with some form of hemophilia of which only a fraction has the funds or the insurance to obtain that kind of treatment in the first place (both the current and the new one)
This was actually the crux of the discussion where I learned about the $50k figure. There are a lot of hemophiliacs in countries that spend, on average, just a few hundred dollars per capita each year on health care. Even if Hemgenix went royalty-free right away and no one ever turned a dollar of profit on it, gene-therapy cures are still inaccessible to the bulk of people the World Federation of Hemophilia represents.
$3.5 million would be like landing on the moon, and $0.05 million would be like a few orbits at ISS height, but they're both astronomical. They're equally out of reach for most people with severe hemophilia.
In fact this is exactly how they set the price for these curative treatments. Gargantuan sums but hypothetically on average cheaper than the overall lifetime costs of living with the disease. Lots of recent debates on this in the world of Hepatitis C.
pricing like that only lasts as long as the patent, the argument being that without the opportunity for that pricing, the research for the drug would not be worthwhile in the first place.
I'm not arguing this is true, but I wouldn't accept a counterargument based on "but it's people, it's people, think of the children"
A more charitable interpretation might be that getting under the cut off is why it's one of the first treatments available. More treatments will become available as the overall costs start beating out the costs of living with $disease.
The recent curative hepatitis treatments have paved the way for this. There are a variety of different approaches including statewide cost sharing funds that pool the cost across all the insurers in the state.
IIRC, single-payer health care systems like the NHS do functionally the exact same thing, which allows them to negotiate significant discounts. I remember reading about a gene therapy for a type of leukodystropphy that was in the millions of dollars, but got negotiated down. 
Yeah you can get a whole genome sequence of yourself for about $300 now.
What companies are offering that at that price?
There are other things that also cause heart disease.
As far as I know, ApoB is the only "necessary but not sufficient" molecule, and that's mostly in LDL. There's also IDL and VLDL, but AFAIK those are in insufficient quantities to have clinical significance - please LMK if you know otherwise. There's also Lp(a), but PCSK9 inhibitors also work there:
> For PCSK9 inhibitors a small reduction of Lp(a) levels could be shown, which was associated with a reduction in cardiovascular events, independently of the effect on LDL cholesterol. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469722/
I hate to sound like I'm only focused on PCSK9i - there's also ezetimibe/bempedoic acid/statins, but AFAIK only PCSK9 has been shown to be a viable target of CRISPR. Perhaps that's your point, but I wonder what would happen if we flattened ApoB starting at age, say, 25. Perhaps the residual Lp(a) wouldn't be enough to cause any MACE.
The argument I have heard for CRISPR are if I recall correctly more about avoiding mutations from "accidental matches" and what that would do to patients and possible descendants.
Okay, so they modify outside of the body and then transplant. So that's why it's sickle cell first, because they can do self-transplantation with bone marrow.
Tests are not mandatory so people do not know or do not care about the problem. Also they should be done before conceiving a child.
That's false... there are mandatory tests the doctors do and they do inform the parents if there is a detected problem.
What tests are you talking about that should be done BEFORE conception!?
Supporting a test that says you have X gene and that might result in a problem so you can't reproduce is a ridiculous stance to have.
You seem to have no knowledge about current medical screenings and no regard for human liberty.
Your description fits my understanding, though I would say social rather than crappy. My point was the implication is you can’t double dip, not that such practices are evil.
In the context of the verse, you're comparing the concept of heavenly rewards with shallow appreciation. I think crappy is appropriate. The verse wasn't teaching that you get an reward either way, but instead that you get a real reward or a worthless 'reward'.
Here are some other counterarguments:
- Most formal drug research, today, is already not worthwhile. The norm is that you spend several billion dollars and recover nothing.
- Most achievements that were worthwhile in retrospect were not worthwhile prospectively. Therefore it is not obvious that things need to be worthwhile prospectively in order to be done. Going into a career as a rock star is, objectively, stupid. But we have a huge supply of wannabe rock stars anyway.
It’s probably one of the precious few arguments where “think of the children” is actually valid.
Nebula genomics, Dante Genomics, ySeq and others (waiting for deals might be needed). 23&me main offering does Not include sequencing.
Shit, 23andme.com's discounted to $99 right now.
Doesn't 23andme only do localized sequencing for particular SNPs that are relevant for genealogical investigation? I didn't think they did full-genome sequencing.
With their history of selling and leaking people's DNA, 23andme doesn't seem like such a great deal at any price.
It is known that infection plays a role in some cases and increasingly suspected that it is a risk factor generally.
Up to 45% of people with chronic infections develop heart disease 10–30 years after the initial illness, which can lead to heart failure.
...gum disease can be caused by 20 to 30 different types of bacteria... and it is increasingly thought that gum disease is probably an independent risk factor for heart disease.
What do you suggest is the mechanism of action behind that? I submit ApoB. Same reason why high blood pressure leads to ASCVD.
Note that risk factor is not causal. I.e. not exercising is a risk factor.
Notably it seems like you can't drive LDL too low https://www.health.harvard.edu/blog/ldl-cholesterol-how-low-...
> What tests are you talking about that should be done BEFORE conception!?
DNA test that detects errors (invalid sequences) known to cause serious illnesses. I think everyone who is considering to have children, should take such a test because he or she can be a carrier of invalid DNA which can be inherited and ruin life for a child. People should behave responsibly.
Not teaching you that you get a reward either way, but it does acknowledge the existence of a reward and it also suggests no penalty. Therefore, if someone was happy to spend money for the social rewards then doing so isn’t discouraged.
You're very off base on your interpretation here-- seeming to try and squeeze the wrong meaning out of a straightforward warning. But it's your right to be wrong, so I'll leave you to it :)
they used to offer full data download but it looks like they disabled that. Nebula Genomics is offering to do it for $500 with black Friday sales, which is close.
Hm. Apparently I was wrong. They indeed "temporarily" disabled it after the credential stuffing attack .
They still do (update: not they are not). It is not and was not a full genome sequencing, but rather a SNP genotyping. Current 23andme raw report (using their v5 chip) contains around 24K SNPs.
Low price genotyping makes me think of the maxim: “ If you are not paying for the product, then you are the product .”
Infection chewing on the heart is a problem.
I don't know why I'm being asked to explicitly state that.
Infection: "not a good thing."
...I feel like we're on different levels so let's just stop here before you start to condescend.
The simplest interpretation isn’t false because a passage includes a deeper meaning.
There’s many things you can take from the crucifixion, but part of the message is being crucified is fatal. And you’re like obviously, but being obvious doesn’t mean something is false.
I'm not condescending. Chagas disease is a class of trypanosomiasis which currently the medical establishment doesn't know how to treat. It's due to a parasite. Parasites living in your heart and feeding on the tissue is not a good thing independent of whether or not it is related to fatty deposits in the vessels.
I'm genuinely baffled that in a discussion of heart disease, actual infection is being handwaved off as irrelevant and only another possible means to cause fatty deposits.
I'm sure our backgrounds are really different. I'm a knowledgeable layperson and a lot of people are dismissive of me because of that.
It doesn't mean your "level" is somehow implicitly above mine anymore than one language is inherently "superior" to another. Language is a tool. Its purpose is communication. If one chooses language that fails to adequately communicate with the target audience, the failure is on the speaker.
Let me add that while I clearly am not as well versed in fatty deposits in the circulatory system as you are, I am leery of any plan to globally suppress any class of molecule.
The brain has the most cholesterol of any organ in the body. If we suppress fats globally to "prevent heart disease," what might this do to the brain?
Bone marrow is fatty. It's a critical part of the immune system where white blood cells are produced. If we suppress fat globally, what does this do to our immune system?
They invented antibiotics not that many decades ago and announced "the end of disease." Fast forward to today and we are wrestling with antibiotic resistant infections and drug shortages.
I'm leery of any claim that "this one neat trick will be the end of this entire class of disease." In this case, I readily know of actual diseases that specific one neat trick wouldn't help at all which are pertinent to the category known as heart disease.
> I'm not condescending.
I encourage you to reflect on your prior statements.
> I'm leery of any claim that "this one neat trick will be the end of this entire class of disease."
Sure, I overspoke. My usage of the word eliminate is strong - there are always edge cases in biology. And I should've been more specific with my language and specified ASCVD instead of the more broad "heart disease". That would, kinda by definition, scope what I'm talking about to fatty deposits. However, I think we're deep in pedantic territory and I hope you forgive me my excess. I didn't mean to enter "one neat trick' territory, though I can see how I came off that way.
I'm also a layman and accept there are gaping holes in my knowledge, which is why I asked you a genuine question: "What do you suggest is the mechanism of action behind that?". My interpretation is that high levels of chronic inflammation leads to endothelial damage which leads to the formation of cholesterol plaques as the immune system attempts to fix the damage it caused. I'm going to assume here that "Infection chewing on the heart is a problem." means you think the parasite literally eats holes in blood vessels? I don't know what you think, which is why I asked. If you know the pathogenesis of heart disease with Chagas, I'd love to learn.
> I am leery of any plan to globally suppress any class of molecule.
A fair concern. I would note that healthy children have an LDL of 23.8 mg/dl https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529694/ and they manage to supply their greedy brains. Note too that circulating (blood) cholesterol is not "global" cholesterol:
> The body has four distinct “pools” of cholesterol, in which tissues have regulatory mechanisms to maintain their respective homeostasis. In order of size, these pools of cholesterol consist of: peripheral tissues, red blood cells, liver, and lipoproteins. It turns out that the brain synthesizes its own cholesterol and does not exchange cholesterol with the other aforementioned pools, which means that cholesterol concentrations outside the brain have no direct impact on brain cholesterol. https://peterattiamd.com/does-low-cholesterol-cause-cognitiv...